Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial

Abstract

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.

Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.

Design, setting, and participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022.

Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy.

Main outcomes and measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours.

Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]).

Conclusions and relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke.

Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Saver reported receiving contracted hourly payments for service on clinical trial steering committees advising on rigorous trial design and conduct from Medtronic, Cerenovus, NeuroVasc, Boehringer Ingelheim (prevention only); stock options for service on Clinical Trial Steering Committees advising on rigorous trial design and conduct from Rapid Medical; and contracted hourly payments for service on data safety monitoring committee advising on rigorous trial design, safety, and conduct from MIVI outside the submitted work. Dr Nogueira reported receiving consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze and being one of the principal investigators of the Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW) trial (funding for this project is provided by Cerenovus) and being an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Vastrax, and Viseon. No other disclosures were reported.

Figures

Figure 1.. Flow of Patients in a Study of the Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy

aOne participant was excluded for metastatic spread of cancer to the brain, 1 was excluded for receiving tirofiban treatment in another hospital, and 1 was excluded for a history of hyperthyroidism that was determined to preclude endovascular treatment. bRandomization was stratified by baseline National Institutes of Health Stroke Scale score (≤17 or >17), occlusion site (the intracranial internal carotid artery or not), and participating center.

Figure 2.. Distribution of Global Disability at 90 Days Based on the Modified Rankin Scale Score

Scores on the modified Rankin Scale for patients in the tirofiban group and the placebo group are shown according to randomization. Scores on the modified Rankin Scale of functional disability range from 0 (no symptoms) to 6 (death). The score was evaluated centrally by 2 modified Rankin Scale–certified neurologists who were blinded to treatment randomization and who reviewed the video or voice recordings elicited using a structured assessment.

Figure 3.. Heterogeneity of Treatment Effect for Less Disability Among Prespecified Subgroups

The forest plot displays effect variation across 8 prespecified subgroups for the adjusted common odds ratio of less disability at 90 days. A lower modified Rankin Scale (mRS) score indicates less disability. The thresholds for age, baseline National Institutes of Health Stroke Scale score, baseline Alberta Stroke Program Early CT Score (ASPECTS), and onset to randomization time were chosen at the median. MCA-M1 and M2 indicate the first and second segments of the middle cerebral artery, respectively. aSalvage therapy was defined as failure of primary means of thrombectomy (eg, stent-retriever or local aspiration) and use of balloon angioplasty and/or stenting. bThe outcome presented was defined as the adjusted common odds ratio for a favorable shift to a lower mRS score at 90 days. Adjusted odds ratios are used for the testing of statistical significance.